S2k guideline for treatment of cutaneous lupus erythematosus - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV).

Cutaneous lupus erythematosus (CLE) is a rare inflammatory autoimmune disease with heterogeneous clinical manifestations. To date, no therapeutic agents have been licensed specifically for patients with this disease entity, and topical and systemic drugs are mostly used 'off-label'. The aim of the present guideline was to achieve a broad consensus on treatment strategies for patients with CLE by a European subcommittee, guided by the European Dermatology Forum (EDF) and supported by the European Academy of Dermatology and Venereology (EADV). In total, 16 European participants were included in this project and agreed on all recommendations. Topical corticosteroids remain the mainstay of treatment for localized CLE, and further topical agents, such as calcineurin inhibitors, are listed as alternative first-line or second-line topical therapeutic option. Antimalarials are recommended as first-line and long-term systemic treatment in all CLE patients with severe and/or widespread skin lesions, particularly in patients with a high risk of scarring and/or the development of systemic disease. In addition to antimalarials, systemic corticosteroids are recommended as first-line treatment in highly active and/or severe CLE. Second- and third-line systemic treatments include methotrexate, retinoids, dapsone and mycophenolate mofetil or mycophenolate acid, respectively. Thalidomide should only be used in selected therapy-refractory CLE patients, preferably in addition to antimalarials. Several new therapeutic options, such as B-cell- or interferon α-targeted agents, need to be further evaluated in clinical trials to assess their efficacy and safety in the treatment of patients with CLE.

The skin in autoimmune diseases-Unmet needs.

Treatment of skin manifestations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) is based on the results of only few randomized controlled trials. The first-line treatment for disfiguring and widespread cutaneous involvement in SLE is antimalarials, but some patients are therapy resistant. Recently, the monoclonal antibody belimumab was approved for SLE as an adjunct therapy for patients with autoantibody-positive disease who despite standard therapy show high disease activity, intolerance of other treatments, or an unacceptably high need for corticosteroids. However, a validated skin score has not been used to confirm the efficacy of belimumab on mucocutaneous manifestations. In SSc, another multi-systemic progressive disease, involvement of the lung, kidney, and the heart is frequently treated with corticosteroids and immunosuppressives, but therapeutic modalities for cutaneous lesions, such as skin sclerosis and digital ulcers, are limited. In the past years, treatment with the endothelin-receptor antagonist bosentan has been proven to reduce the occurrence of new digital ulcers in SSc patients but has no or limited effect on healing of digital ulcers. DM is an idiopathic autoimmune disease characterized by inflammation of the muscles and skin, which is treated with immunosuppressives. Corticosteroids are the first-line treatment for muscle involvement in DM, but skin lesions often flare by reduction or discontinuation. In summary, there is a high unmet need for new therapeutic strategies focusing on skin involvement in systemic autoimmune diseases. Therefore, innovative designs of randomized controlled trials with validated skin scores are warranted to develop new therapeutic strategies for patients with cutaneous manifestations.

Advances in the treatment of cutaneous lupus erythematosus.

Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE.

Fumaric acid ester treatment in cutaneous lupus erythematosus (CLE): a prospective, open-label, phase II pilot study.

OBJECTIVE: The aim of the study was to assess the efficacy and safety of fumaric acid esters (FAEs) in patients with cutaneous lupus erythematosus (CLE). METHODS: In this 24-week, prospective, open-label, phase II pilot study, 11 patients with CLE, refractory to topical corticosteroids, were included. The primary endpoint of the study was the evaluation of the efficacy of FAEs after 24 weeks of treatment as assessed by the Revised Cutaneous Lupus Disease Area and Severity Index (RCLASI). RESULTS: Compared to baseline, significant improvement in the mean total RCLASI activity score and the mean RCLASI activity score for skin lesions was observed in week 12 (p = 0.002, p = 0.002, respectively) and in week 24 (p = 0.009, p = 0.009, respectively). Most common adverse events included abdominal cramps and headache. CONCLUSIONS: FAEs could be an alternative and safe treatment in patients with therapy-refractory CLE; however, randomized controlled trials are warranted to evaluate the efficacy and safety of FAEs in this disease.

Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus: analysis of 1002 patients from the EUSCLE database.

BACKGROUND: In recent years it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents. OBJECTIVES: To investigate the influence of smoking on disease severity and antimalarial treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). METHODS: A total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries. Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment. RESULTS: A high percentage (87·2%) of the 499 patients with CLE, who have ever smoked, had already smoked at the date of their first diagnosis. Patients with intermittent CLE have ever smoked significantly more often than patients with subacute CLE (P < 0·05) and chronic CLE (P < 0·05). The total CLASI activity and damage score of patients with CLE was 6·6 ± 7·1 and 2·6 ± 4·3, respectively, and was higher in patients who have ever smoked than in nonsmokers. Antimalarial treatment was successful in 84·3% of cases, with a significantly higher efficacy in nonsmokers than in patients with CLE who have ever smoked (P < 0·05). CONCLUSIONS: This analysis of a multicentre study population of 838 patients with CLE assessed by the EUSCLE Core Set Questionnaire confirms that smoking negatively influences CLE disease severity and the efficacy of antimalarial treatment.

[Nature or nurture: effects of parental ametropia on children's refractive errors]. / Anlage versus Umwelt: Wie stark sind Ametropien angeboren?

PURPOSE: The aim of this study was to quantify the degree of association between juvenile refraction errors and parental refraction status. METHODS: Using a simple questionnaire we conducted a cross-sectional study to determine the prevalence and magnitudes of refractive errors and of parental refraction status in a sample (n=728) of 10- to 18-year-old Austrian grammar school students. RESULTS: Students with myopia or hyperopia were more likely to have ametropic parents and refraction was more myopic in juveniles with one or two parents being ametropic. The prevalence of myopia in children with 2 ametropic parents was 54%, decreasing to 35% in pupils with 1 and to 13% in children with no ametropic parents. The odds ratio for 1 and 2 compared with no ametropic parents was 8.3 and 3.7 for myopia and 1.3 and 1.6 for hyperopia, respectively. Furthermore, the data indicate a stronger influence of the maternal ametropia on children's refractive errors than paternal ametropia. CONCLUSIONS: Genetic factors play a significant role in refractive error and may be of dominant influence for school myopia under conditions of low environmental variation.